Maxim Pharmaceuticals has discovered a natural product (MX2060), which is an inducer of caspase-mediated apoptosis, through its cancer drug screening program. The experiments proposed in this grant and the results from the Phase 1 study warrant the next series of preclinical studies needed to advance MX2060, or an analog toward clinical trials. The primary emphasis of the Phase II is the selection of an analog for development, and all aims are proposed to specifically address this goal. The isolation and characterization of the MX2060 binding protein will provide exciting opportunities with this compound's unique mechanism of action. MX2060, has certain unique features: its rapid induction of apoptosis, its effectiveness on cells overexpressing cell survival genes and in vivo therapeutic index, despite its effectiveness on quiescent tumor cells, all indicating a potential application to a broad range of cancers. Compounds derived from natural products have played an important role in drug discovery. This is especially true in the cancer field: at least half of the chemotherapeutic drugs currently in use are natural products, or natural product analogues. MX2060 potentially represents a completely new class of drug treatment for cancer and, therefore, may address the enormous unmet need for innovative cancer therapies. [unreadable] [unreadable] [unreadable]